Agrin as a Stable Biomarker for Muscle Strength Decline in Elderly Sarcopenic Patients Associated with Neuromuscular Junction Dysfunction.

Abstract

Agrin-mediated neuromuscular junction (NMJ) morphological alterations is one of the main pathogeneses of sarcopenia. The aim of this study was to observe the changes in serum agrin in patients with different degrees of sarcopenia and the alterations in Agrin receptors in human skeletal muscle with age. A total of 236 elderly subjects were enrolled and categorized into nonsarcopenia, possible sarcopenia, sarcopenia, and severe sarcopenia groups. Serum levels of the C-terminal Agrin fragment were quantified using an Enzyme-Linked Immunosorbent Assay (ELISA) kit. In addition, in a distinct and smaller exploratory subgroup (n = 12), quantitative real-time polymerase chain reaction and immunofluorescence staining were performed to investigate the expression of Agrin receptors, specifically low-density lipoprotein receptor-related protein 4 (Lrp4) and alpha-dystroglycan (α-DG), in human skeletal muscle samples. Compared with that in the nonsarcopenia group, the level of agrin in the other groups was significantly different. Partial correlation analysis and binary logistic regression analysis suggested that the level of Agrin was associated with handgrip strength. There was a significant increase in the serum level of agrin and a reduction in the mRNA expression of the agrin receptors Lrp4, α-DG, and RAPSN, while immunofluorescence analysis confirmed the expression patterns of the Lrp4 and α-DG receptors. In the elderly population, the level of agrin decreased in patients with sarcopenia, while the expression of its receptors also decreased. These factors result in NMJ morphological alterations, weakened muscle contraction, and increased risk of sarcopenia.